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Wellcome-MRC Cambridge Stem Cell Institute

Diabetes drug reverses cell ageing and could stop multiple sclerosis

New research published in Cell Stem Cell suggests a common diabetes drug could hold the key to stopping disease progression in multiple sclerosis (MS). The new finding offers hope to people living with advanced forms of the condition, who currently have no treatment and often see disability as inevitable.

The MS Society funded research suggests alternate day fasting – and the fasting mimetic drug metformin, already used worldwide to treat diabetes – could be the answer to stopping MS, through its ability to restore cells to a younger, healthier state.

Studying rats, researchers Wellcome - MRC Cambridge Stem Cell Institute (University of Cambridge) found the drug was able to return cells to a “more youthful state”, and encourage the re-growth of myelin – the fatty sheath that surrounds our nerves, which is damaged in MS. Myelin regenerative treatments are considered essential to stop disease progression in MS, but achieving this goal has been elusive.

Now for the first time the scientists have discovered that the reduced regenerative capacity of stem cells (called oligodendrocyte progenitor cells, or OPCs),  in people with progressive forms of MS is down to things that happen to everyone as we age, including reduced metabolic function and increased DNA damage. The researchers found both fasting and treatment with metformin could reverse these changes, and restore the regenerative capacity of OPCs, which are responsible for making myelin in the body.

The research was led by Professor Robin Franklin and Dr Björn Neumann.

Professor Franklin said: “As with most regenerative processes, our body’s ability to repair myelin declines as we age. The failure to regenerate lost cells called oligodendrocytes is associated with irreversible degeneration in MS, so regenerative therapies have been a long sought after but elusive goal. This is one of the most significant advances in myelin repair therapies there has ever been.

“The findings shed light on why cells lose their ability to regenerate myelin, and how this process might be reversed. Although research so far has been done in rats, we hope to move it forward into humans soon. MS is relentless, painful, and disabling, and – while it’s early days – this discovery could lead us to vital new treatment targets for progressive forms of the condition.”

Normally OPCs develop into oligodendrocytes, which produce myelin. But as we age they are less likely to do this, so there is a reduction in myelin repair. When researchers treated older rats with metformin, OPCs recovered their ability to change into oligodendrocytes. This was able to improve remyelination, giving us an important new insight for how we might finally treat progressive forms of MS.

MS Society Director of Research, Dr Susan Kohlhaas, said: “More than 100,000 people live with MS in the UK and many don’t have treatment. The treatments that do exist only work on the immune system, and only help people with the relapsing form of the condition. We can see a future where nobody needs to worry about MS getting worse, or eventually needing a wheelchair, but for this to happen we need treatments that repair myelin.

“Professor Franklin’s research demonstrates myelin repair therapies are within our grasp, and we’re closer than ever to finding treatments for everyone living with MS.”

Publication details:

Bjoern Neumann, Roey Baror, Chao Zhao, Michael Segel, Sabine Dietmann, Khalil Rawji, Sarah Foerster, Crystal McClain, Kevin Chalut, Peter van Wijngaarden, Robin FranklinMetformin restores CNS remyelination capacity by rejuvenating aged stem cells is published in Cell Stem Cell.